Dr Hilary Martin | Group leader

Martin, Hilary

My work focuses on the analysis of high-throughput sequence and genotype data from large cohorts to address various medical and population genetic questions.

I recently became a Group Leader in Human Genetics (September 2018). My new group will study population and medical genetics in populations with high consanguinity, to learn about genetic architecture of different traits and how demography and selection have shaped the distribution of disease-causing variation in these populations.

As a postdoc at Sanger, my major focus was on exploring genetic architecture in the Deciphering Developmental Disorders (DDD) study, a large cohort of exome-sequenced individuals with rare developmental disorders. I quantified the contribution of recessive coding variats to the cohort and found that they account for a surprisingly small fraction of patients (Figure 1; see our recent paper in Science). I also worked closely with Mari Niemi and Jeff Barrett on the role of common variation in the DDD. In this paper in Nature, we demonstrated that the same common SNPs that contribute to psychiatric traits and cognition in the general population also increase risk of these rare disorders generally thought to be monogenic. Future work will include exploring the contribution of more complex genetic architectures in these rare disorders, and the interplay between common and rare variants.

Estimates of the contribution of recessive and de novo dominant coding variants to different groups of probands within the DDD study, in either known or as-yet-undiscovered genes.

Levels of autozygosity in the East London Genes and Health cohort, stratified by ancestry and reported parental relatedness.

Additionally, as part of the East London Genes and Health Project, I am analysing exome-sequence data from British South Asian individuals with high levels of parental relatedness. These individuals are highly enriched for homozygous loss-of-function mutations that can be informative about gene function and, potentially, new drug targets, and we are piloting recall-by-genotype studies to investigate some of these. They also have high rates of certain complex diseases (e.g. type 2 diabetes), and we are investigating the genetic architecture of these diseases compared to European populations.